The background description includes information that may be useful in understanding the present invention. It is not an admission that any of the information provided herein is prior art or relevant to the presently claimed invention, or that any publication specifically or implicitly referenced is prior art.
Mammalian pattern recognition receptors (PRR) serve a critical role in maintaining healthy tissue homeostasis as sensors of microbial invaders and otherwise diseased/damaged cells. At the present time, mammalian PRR proteins are believed to be comprised of members of the toll-like receptors (TLR), C-type lectin receptors (CLR), NOD-like receptors (NLR), the RNA helicases belonging to the RIG-I-like receptor family (RLR), and secreted PRR including members of the blood complement proteins.
Perhaps the best studied of the group, TLR (which includes 10 different isotypes in man, 13 in mice) are membrane-bound proteins which recognize both pathogen-associated molecular patterns (PAMPs) as well as damage-associated molecular patterns (DAMPs). Some examples of PAMPs recognized by TLR are provided by the recognition of bacterial endotoxin by TLR4, di- and tri-acylated peptides by TLR2 containing protein complexes, viral double stranded RNA by TLR3, flagellin by TLR5, the nucleotide analog imiquimod recognition by TLR7, and CpG containing deoxyribonucleic acids (DNA) by TLR9. Sterile-injury produced DAMPs include the high-mobility group box-1 protein HMGB1, members of the heat shock protein family like HSP22, HSP70, HSP72, and gp96, or components of the extracellular matrix including such as biglycan, tenascin-C, versican, and oligosaccharides derived from hyaluronic acid and heparan sulfate. To date, TLR2 and TLR4 are believed to act as the main receptors for DAMPs.
However, while the role of PRR in numerous physiological processes, and particularly in processes associated with inflammation and immune activation has become increasingly studied, therapeutic and/or prophylactic use of such agents and their ligands has been elusive. Thus, there is still a need to provide improved therapeutic and prophylactic compositions related to PRR.